Curcumin Protects Neurons Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury Through Activation of Peroxisome Proliferator-Activated Receptor-c Function
Curcumin Protects Neurons Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury Through Activation of Peroxisome Proliferator-Activated Receptor-c Function
复制标题
姜黄素通过激活过氧化物酶体增殖物激活受体-c 功能，保护神经元免受缺氧/复氧引起的损伤
DOI：
10.1002/jnr.23438
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发表时间：
2014-11-01
影响因子：
4.2
通讯作者：
Wang, Yu
中科院分区：
文献类型：
--
作者：
Liu, Zun-Jing;Liu, Hong-Qiang;Wang, Yu
姜黄衍生物姜黄素对脑缺血损伤的保护作用。我们以前证明，姜黄素激活过氧化物酶体增殖物激活受体-γ（PPAR γ），一种参与神经保护和抗炎信号通路的配体激活转录因子。本研究测试了姜黄素对大鼠皮层神经元氧-葡萄糖剥夺/再给氧（OGD/R）诱导的损伤的神经保护作用是否（至少部分）由PPAR γ介导。姜黄素（10 μ M）有效地增强OGD/R后的PPAR γ表达和转录活性。此外，姜黄素显着增加神经元的活力，证明了减少乳酸脱氢酶的释放和减少一氧化氮的生产，半胱天冬酶-3活性，和凋亡。这些保护作用被抑制的共同管理的PPAR γ拮抗剂2-氯-5-硝基苯甲酰苯胺（GW 9662），并通过预先转染的小干扰RNA（siRNA）靶向PPAR γ，治疗，对健康的神经元没有毒性作用。姜黄素减少OGD/R诱导的活性氧的积累，抑制线粒体凋亡途径，细胞色素c和凋亡诱导因子的释放减少和线粒体膜电位和Bax/Bcl-2比值的维持。同样，GW 9662或PPAR γ siRNA转染减轻了姜黄素对线粒体功能的保护作用。姜黄素抑制I κ B激酶磷酸化和I κ B降解，从而抑制核因子-κ B（NF-κ B）核转位，其作用也被GW 9662或PPAR γ siRNA阻断。免疫沉淀实验表明，PPAR γ与NF-κ B p65相互作用，抑制NF-κ B活化。本研究提供了强有力的证据，证明姜黄素对OGD/R的神经保护作用中至少有一部分是由PPAR γ激活介导的。(C)2014 Wiley Periodicals，Inc.
The turmeric derivative curcumin protects against cerebral ischemic injury. We previously demonstrated that curcumin activates peroxisome proliferator-activated receptor-gamma (PPAR gamma), a ligand-activated transcription factor involved in both neuroprotective and anti-inflammatory signaling pathways. This study tested whether the neuroprotective effects of curcumin against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury of rat cortical neurons are mediated (at least in part) by PPAR gamma. Curcumin (10 mu M) potently enhanced PPAR gamma expression and transcriptional activity following OGD/R. In addition, curcumin markedly increased neuronal viability, as evidenced by decreased lactate dehydrogenase release and reduced nitric oxide production, caspase-3 activity, and apoptosis. These protective effects were suppressed by coadministration of the PPAR gamma antagonist 2-chloro-5-nitrobenzanilide (GW9662) and by prior transfection of a small-interfering RNA (siRNA) targeting PPAR gamma, treatments that had no toxic effects on healthy neurons. Curcumin reduced OGD/R-induced accumulation of reactive oxygen species and inhibited the mitochondrial apoptosis pathway, as indicated by reduced release of cytochrome c and apoptosis-inducing factor and maintenance of both the mitochondrial membrane potential and the Bax/Bcl-2 ratio. Again, GW9662 or PPAR gamma siRNA transfection mitigated the protective effects of curcumin on mitochondrial function. Curcumin suppressed I kappa B kinase phosphorylation and I kappa B degradation, thereby inhibiting nuclear factor-kappa B (NF-kappa B) nuclear translocation, effects also blocked by GW9662 or PPAR gamma siRNA. Immunoprecipitation experiments revealed that PPAR gamma interacted with NF-kappa B p65 and inhibited NF-kappa B activation. The present study provides strong evidence that at least some of the neuroprotective effects of curcumin against OGD/R are mediated by PPAR gamma activation. (C) 2014 Wiley Periodicals, Inc.